Comparison of Pharmacokinetics of Enrofloxacin After Single Oral Bolus and Pulse Dose Administration in Broiler Chicken

Enrofloxacin was administered to commercial broiler chicken of 6 weeks of age at 10 mg kg^?1 as oral bolus and pulse dose to two groups of twelve birds each. Blood was collected at predetermined time interval and plasma samples were analyzed for enrofloxacin concentration by using HPLC. Mean plasma concentration was significantly higher in oral bolus dose up to 2 h and at 48 h. In both the groups enrofloxacin concentration was above 0.30 μg mL^?1 up to 24 h. Pharmacokinetic parameters were calculated by non compartmental analysis which revealed significant increase in AUC_0–∞ (25.35 ± 1.92 vs. 19.66 ± 1.68 μg h mL^?1) and t_1/2β (10.63 ± 0.35 vs. 8.70 ± 0.74 h) in oral bolus dose when compared to pulse dose. There was no significant difference in other pharmacokinetic parameters such as MRT, MAT, V_{d area}/F, V_dss/F, Cl_B/F, C_max and t_max. Hence it can be concluded that enrofloxacin administered to broiler chicken at 10 mg kg^?1 every 24 h as pulse dose will result in better clinical efficacy at par with oral bolus dose.     

Effect of Boron on the Contents of Chlorophyll,Carotenoid, Phenol and Soluble Leaf Protein in Mung Bean,Vigna radiata (L.) Wilczek

Greenhouse experiments were carried out to study the effect of boron (B) on certain biochemical constituents considering mung bean, Vigna radiata (L.) Wilczek as an experimental crop. B as boric acid (H₃BO₃) was applied at the concentrations of 0, 1, 2, 4, 8, 16 and 32 μg B g^?1 soil. Lower applied doses of B up to 4 μg g^?1 resulted in an increase in chlorophyll and carotenoid contents and decrease in stress indicators viz. total phenol content and soluble leaf protein content. Maximum increment in chlorophyll and carotenoid contents was observed at 4 μg g^?1 B concentrations, while at this concentration (4 μg g^?1) maximum decrease in total phenol content and soluble leaf protein content was observed. Reciprocal relationship between total chlorophyll contents and total phenol content was observed. Adverse effect on selected biochemical constituents beyond 4 μg g^?1 B concentrations reflected the importance of efficient and appropriate use of boron in agronomic practices for mung bean.     

Comparing hemodynamic effects with three different measurement devices, of two methods of external leg compression versus passive leg raising in patients after cardiac surgery

External leg compression (ELC) may increase cardiac output (CO) in fluid-responsive patients like passive leg raising (PLR). We compared the hemodynamic effects of two methods of ELC and PLR measured by thermodilution (COtd), pressure curve analysis Modelflow? (COmf) and ultra-sound HemoSonic? (COhs), to evaluate the method with the greatest hemodynamic effect and the most accurate less invasive method to measure that effect. We compared hemodynamic effects of two different ELC methods (circular, A (n = 16), vs. wide, B (n = 13), bandages inflated to 30 cm H₂O for 15 min) with PLR prior to each ELC method, in 29 post-operative cardiac surgical patients. Hemodynamic responses were measured with COtd, COmf and COhs. PLR A increased COtd from 6.1 ± 1.7 to 6.3 ± 1.8 L·min^?1 (P = 0.016), and increased COhs from 4.9 ± 1.5 to 5.3 ± 1.6 L·min^?1 (P = 0.001), but did not increase COmf. ELC A increased COtd from 6.4 ± 1.8 to 6.7 ± 1.9 L·min^?1 (P = 0.001) and COmf from 6.9 ± 1.7 to 7.1 ± 1.8 L·min^?1 (P = 0.021), but did not increase COhs. ELC A increased COtd and COmf as in PLR A. PLR B increased COtd from 5.4 ± 1.3 to 5.8 ± 1.4 L·min^?1 (P < 0.001), and COhs from 5.0 ± 1.0 to 5.4 ± 1.0 L·min^?1 (P = 0.013), but not COmf. ELC B increased COtd from 5.2 ± 1.2 to 5.4 ± 1.1 L·min^?1 (P = 0.003), but less than during PLR B (P = 0.012), while COmf and COhs did not change. Bland–Altman and polar plots showed lower limits of agreement with changes in COtd for COmf than for COhs. The circular leg compression increases CO more than bandage compression, and is able to increase CO as in PLR. The less invasive Modelflow? can detect these changes reasonably well.     

Evaluation of three measures of cardiorespiratory fitness in independently ambulant stroke survivors

Measuring cardiorespiratory fitness (CRF) in the stroke population is challenging. Currently, the recommended method is a graded exercise test (GXT) on an ergometer such as a treadmill or cycle, which may not always be possible. We investigated whether walking tests such as the six-minute walk test (6MWT) and the shuttle walk test (SWT) may be appropriate indicators of CRF in the stroke population. Twenty-three independently ambulant stroke survivors (11 men, age 61.5 ± 18.4 years) within one-year post stroke performed the 6MWT, SWT, and cycle GXT, during which peak oxygen consumption (VO_2peak) and heart rate (HR_peak) were recorded. There were no differences (p > 0.05) in mean VO_2peak among the three tests (min-max: 17.08–18.09 mL kg^?1 min^?1). For individuals, small discrepancies in VO_2peak between the 6MWT and other tests were greater with higher fitness levels. HR_peak was significantly (p = 0.005) lower during the 6MWT. Correlations between VO_2peak and performance measures within each test were high (6MWT VO_2peak and distance: r = 0.78, SWT VO_2peak and shuttles: r = 0.73, cycle GXT VO_2peak and workload: r = 0.77) suggesting the performance measures may be clinically useful as proxy measures of CRF. Common comorbidities, such as lower-limb joint pain and poor balance, and participant’s fastest walking speed, should inform the choice of CRF test.     

The potential of Sentinel-2 data for estimating biophysical variables in a boreal forest: a simulation study

In this study we use ground reference data from 962 forest plots to demonstrate the potential of Sentinel-2 (S2) bands in estimating canopy biophysical properties in boreal forests in Finland. We simulated canopy bidirectional reflectance factors (BRFs) using the PARAS model, which applies photon recollision probability. Results showed that the highest correlation between simulated S2 BRFs and fraction of absorbed photosynthetically active radiation (fPAR) was for the band combination band 7/band 9 (wavelengths 773–793 nm and 935–955 nm, respectively) (the coefficient of determination (R²) was 0.93). For effective leaf area index (LAI_e) the best band combination was band 8/band 4 (wavelengths 785–900 nm and 650–680 nm, respectively) (R² = 0.93). Based on this study, the above-ground biomass (AGB) and S2 band combinations did not show strong relationships (R² = 0.24). The new inverted red-edge chlorophyll index (IRECI) and Sentinel-2 red-edge position – index (S2REP) showed moderate relationships with fPAR (R² = 0.61 and R² = 0.45, respectively) and LAI_e (R² = 0.56 and R² = 0.30, respectively). This study demonstrated the potential of the S2 data to estimate canopy biophysical properties.     

Progression of diffuse myocardial fibrosis assessed by cardiac magnetic resonance T1 mapping

To evaluate long-term changes in diffuse myocardial fibrosis using cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) and T₁ mapping. Patients with chronic stable cardiomyopathy and stable clinical status (n = 52) underwent repeat CMR at a 6 month or greater follow up interval and had LGE and left ventricular (LV) T₁ mapping CMR. Diffuse myocardial fibrosis (excluding areas of focal myocardial scar) was assessed by post gadolinium myocardial T₁ times. Mean baseline age of 52 patients (66 % male) was 35 ± 19 years with a mean interval between CMR examinations of 2.0 ± 0.8 years. CMR parameters, including LV mass and ejection fraction, showed no change at follow-up CMR (p > 0.05). LVT₁ times (excluding focal scar) decreased over the study interval (from 468 ± 106 to 434 ± 82 ms, p = 0.049). 38 Patients had no visual LGE?, while 14 were LGE+. For LGE? patients, greater change in LV mass and end systolic volume index were associated with change in T₁ time (β = ?2.03 ms/g/m², p = 0.035 and β = 2.1 ms/mL/m², p = 0.029, respectively). For LGE+ patients, scar size was stable between CMR1 and CMR2 (10.7 ± 13.8 and 11.5 ± 13.9 g, respectively, p = 0.32). These results suggest that diffuse myocardial fibrosis, as assessed by T₁ mapping, progresses over time in patients with chronic stable cardiomyopathy.     

Non-invasive measurement of cardiac output in obese children and adolescents: comparison of electrical cardiometry and transthoracic Doppler echocardiography

The objective of this study was to evaluate the reliability and accuracy of electrical cardiometry (EC) for the noninvasive determination of cardiac output (CO) in obese children and adolescents. We compared these results with those obtained by transthoracic echocardiography. Sixty-four participants underwent simultaneous measurement of CO. Cardiac output was measured by EC using the ICON^® device. Simultaneously CO was determined by using transthoracic Doppler echocardiography from parasternal long-axis and apical view. The median age was 12.52 years (range 7.9–17.6 years) and 36 (56 %) were female. A strongly significant correlation was found between the CO_EC and CO_Echo measurements (p < 0.0001, r = 0.91). Significant correlations were also found between CO and age (r = 0.37, p = 0.002), weight (r = 0.57, p < 0.0001), height (0.60, p < 0.0001) and BMI (r = 0.42, p = 0.001). The mean difference between the two methods (CO_EC ? CO_Echo) was 0.015 l min^?1. According to the Bland and Altman method, the upper and lower limits of agreement, defined as mean difference ±2 SD, were +1.21 and ?0.91 l min^?1, respectively. Compared to the transthoracic Doppler echocardiography, Electrical Cardiometry provides accurate and reliable CO measurements in obese children and adolescents.     

Acute hyperinsulinaemia decreases cholesterol synthesis less in subjects with non-insulin-dependent diabetes mellitus than in non-diabetic subjects

To investigate the effect of insulin on cholesterol synthesis in vivo we measured plasma mevalonic acid (MVA) concentrations using gas chromatography–mass spectrometry in six non-obese patients with non-insulin-dependent diabetes mellitus (NIDDM) [four men, two women; age 57.5±2.2 years (mean±SEM); glycated haemoglobin (HbA1) 8.5±0.5%; total cholesterol (TC) 5.7±0.5 mmol L^?1, triglyceride (TG) 3.8±0.9 mmol L^?1] and six non-diabetic, sex- and age-matched control subjects (age 55.7±2.8 years; HbA1 6.5±0.1%; TC 5.4±0.3 mmol L^?1, TG 1.2±0.1 mmol L^?1). Subjects were studied twice: during 13-h hyperinsulinaemic (1 mu kg^?1 min^?1), euglycaemic (5 mmol L^?1) clamp and during a saline infusion. Baseline MVA concentration was significantly higher in diabetic patients than in control subjects (9.8±0.7 ng mL^?1 vs. 5.6±0.9 ng mL^?1P=0.004). At the end of each study, MVA concentration, expressed as a percentage of baseline, was significantly lower during the hyperinsulinaemic, euglycaemic clamp than during the saline study in both the diabetic (54.4±5.3% vs. 69.6±6.3%, P=0.036) and control subjects (30.5±3.4% vs. 61.7±6.0%, P=0.01). However, the decrease in MVA during the hyperinsulinaemic clamp study was more marked in the control subjects than in the diabetic subjects (P=0.03). A significant positive correlation was found between percentage decrease of MVA and non-esterified fatty acids following the insulin clamp in NIDDM (r=0.83, P=0.04). We conclude that acute hyperinsulinaemia decreases cholesterol synthesis less in subjects with NIDDM than in non-diabetic subjects and that this phenomenon, together with increased basal cholesterol synthesis in NIDDM, may in part be due to insulin resistance.     

Effect of glibenclamide on insulin release at moderate and high blood glucose levels in normal man

Insulin release occurs in two phases; sulphonylurea derivatives may have different potencies in stimulating first- and second-phase insulin release. We studied the effect of glibenclamide on insulin secretion at submaximally and maximally stimulating blood glucose levels with a primed hyperglycaemic glucose clamp. Twelve healthy male subjects, age (mean ± SEM) 22.5 ± 0.5 years, body mass index (BMI) 21.7 ± 0.6 kg m^?2, were studied in a randomized, double-blind study design. Glibenclamide 10 mg or placebo was taken before a 4-h hyperglycaemic clamp (blood glucose 8 mmol L^?1 during the first 2 h and 32 mmol L^?1 during the next 2 h). During hyperglycaemic clamp at 8 mmol L^?1, the areas under the Δinsulin curve (AUC_Δinsulin , mean ± SEM) from 0 to 10 min (first phase) were not different: 1007 ± 235 vs. 1059 ± 261 pmol L^?1 × 10 min (with and without glibenclamide, P = 0.81). However, glibenclamide led to a significantly larger increase in AUC_Δinsulin from 30 to 120 min (second phase): 16 087 ± 4489 vs. 7107 ± 1533 pmol L^?1 × 90 min (with and without glibenclamide respectively, P < 0.03). The same was true for AUC_ΔC-peptide: no difference from 0 to 10 min but a significantly higher AUC_ΔC-peptide from 30 to 120 min on the glibenclamide day (P < 0.01). The M/I ratio (mean glucose infusion rate divided by mean plasma insulin concentration) from 60 to 120 min, a measure of insulin sensitivity, did not change: 0.26 ± 0.05 vs. 0.22 ± 0.03 μmol kg^?1 min^?1 pmol L^?1 (with and without glibenclamide, P = 0.64). During hyperglycaemic clamp at 32 mmol L^?1, the AUC_Δinsulin from 120 to 130 min (first phase) was not different on both study days: 2411 ± 640 vs. 3193 ± 866 pmol L^?1 × 10 min (with and without glibenclamide, P = 0.29). AUC_Δinsulin from 150 to 240 min (second phase) also showed no difference: 59 623 ± 8735 vs. 77389 ± 15161 pmol L^?1 × 90 min (with and without glibenclamide, P = 0.24). AUC_ΔC-peptide from 120 to 130 min and from 150 to 240 min were slightly lower on the glibenclamide study day (both P < 0.04). The M/I ratio from 180 to 240 min did not change: 0.24 ± 0.04 vs. 0.30 ± 0.07 μmol kg^?1 min^?1 pmol L^?1 (with and without glibenclamide, P = 0.25). In conclusion, glibenclamide increases second-phase insulin secretion only at a submaximally stimulating blood glucose level without enhancement of first-phase insulin release and has no additive effect on insulin secretion at maximally stimulating blood glucose levels. Glibenclamide did not change insulin sensitivity in this acute experiment.     

Arterial antithrombotic and bleeding time effects of apixaban,a direct factor Xa inhibitor,in combination with antiplatelet therapy in rabbits

Summary. Background: Optimal treatment of arterial thrombosis may include a combination of antiplatelet and anticoagulant drugs. We evaluated apixaban, a direct and highly selective factor Xa inhibitor, in combination with clinically relevant doses of aspirin and/or clopidogrel for prevention of arterial thrombosis in rabbits. Methods: Studies were conducted in rabbit models of electrically induced carotid artery thrombosis and cuticle bleeding time (BT). Apixaban 0.04 and 0.3 mg kg^?1 h^?1 or aspirin 1 mg kg^?1 h^?1 was infused intravenous (i.v.) continuously from 1 h before artery injury or cuticle bleed until the end of the experiment. Clopidogrel at 3 mg kg^?1 was dosed orally once daily for three days, with the last dose given 2 h before injury. Results: Control thrombus weight and BT averaged 8.6 ± 0.9 mg and 181 ± 12 s, respectively (n = 6 per group). Effective doses of apixaban that reduced thrombus weight by 20 and 50% (ED₂₀ and ED₅₀) were 0.04 and 0.3 mg kg^?1 h^?1 i.v., respectively. Addition of aspirin to apixaban ED₂₀ and ED₅₀ significantly reduced the thrombus weight from 7.4 ± 0.5 to 5.3 ± 0.3 and 3.6 ± 0.3 mg, respectively, with no significant increases in BT (190 ± 7 s vs.181 ± 9 and 225 ± 11 s, respectively). Addition of aspirin and apixaban (ED₂₀ dose) to clopidogrel produced a further significant reduction in thrombus weight from 5.3 ± 0.3 to 0.7 ± 0.1 mg. This combination of clopidogrel and aspirin with apixaban (ED₂₀ dose) produced a significant but moderate BT increase of 2.1 times control. Conclusions: The combination of apixaban and aspirin or apixaban, aspirin and clopidogrel can reduce formation of occlusive arterial thrombosis without excessive increases in BT in rabbits.     

Estimating dry matter content of fresh leaves from the residuals between leaf and water reflectance

At about 1720 nm wavelength, there is an absorption feature of leaf dry matter based on a C?H stretch overtone, which is difficult to detect in fresh green leaves because of the absorption spectrum of liquid water. We applied a method originally proposed in Remote Sensing of Environment by B.-C. Gao and A.F.H. Goetz (Estimating dry matter content of fresh leaves from the residuals between leaf and water reflectance, pp. 137–145, 1994) that used linear regression between the natural logarithm of leaf spectral reflectance and the specific absorption coefficient of liquid water over wavelengths from 1500 to 1800 nm to calculate an expected reflectance spectrum. The residual difference between the measured and expected leaf reflectance spectra enhanced the absorption feature of dry matter. The absorption feature was quantified using the normalized dry matter index (NDMI) based on the contrast between the residual leaf reflectance at 1649 and 1722 nm. NDMI was linearly related to leaf dry matter content (g cm^?2) for data obtained in the field (coefficient of determination r ² = 0.636) and for the leaf optical properties experiment (LOPEX; r ² = 0.684). Lignin and cellulose contents were also measured during LOPEX, but NDMI was weakly correlated to these variables, indicating NDMI was sensitive to all leaf biochemical constituents. Estimation of dry matter content combined with estimates of water content will facilitate the calculation of the fuel moisture content for prediction of wildfire.     

Relationship between endothelial vasomotor function and strut coverage after implantation of drug-eluting stent assessed by optical coherence tomography

The use of drug-eluting stent (DES) has been associated with incomplete endothelialization and coronary endothelial dysfunction. However, the relationship between endothelial vasomotor function and strut coverage evaluated by optical coherence tomography (OCT) has not been sufficiently assessed. Therefore, we evaluated the relationship between endothelial vasomotor function and the degree of stent strut coverage after DES implantation. Coronary angiography and OCT were performed in 112 patients at the 6-month follow-up after DES implantation. The patients were divided into tertiles according to the degree of strut coverage as was assessed by OCT. Endothelial vasomotor function was evaluated with intracoronary infusion of incremental doses of acetylcholine (Ach; 10^?8–10^?6 mol/L). Vascular responses at the proximal and distal segments to the stent margin were evaluated by quantitative coronary angiography analysis before and after Ach infusion. The percentage of uncovered struts in tertiles 1–3 was 4.2 ± 3.3, 17.3 ± 4.2 and 44.5 ± 14.4 %, respectively, (p < 0.001). The percentage of maximal vasoconstriction in tertiles 1–3 was 8.3, 9.1 and 8.1 % at proximal segment to the stent margin (p = 0.95), respectively, and 13.9, 11.1 and 14.2 % at distal segment to the stent margin (p = 0.74), respectively. The percentage of uncovered struts was not correlated with the degree of vasomotor function (r = ?0.01, p = 0.92 at the proximal segment; r = ?0.07, p = 0.47 at the distal segment). The percentage of strut coverage was not associated with the degree of abnormal vasoconstriction in response to intracoronary infusion of Ach 6 months after DES implantation.     

Growth,Physiology and Biochemical Responses of Two Different <Emphasis Type="Italic">Brassica</Emphasis> Species to Elevated CO<Subscript>2</Subscript>

In an open top chamber study, two contrasting Brassica cultivars from two different species were grown under two distinct levels of CO₂ concentration, 550 µmol mol^?1 (elevated) and 390 µmol mol^?1 (ambient). CO₂ enrichment showed significant increase in growth, leaf area and dry matter production in both the species. The continuous higher rate of photosynthesis (36.2 % in RH-30 and 27.3 % in Pusa Gold) under elevated CO₂ condition attributed to the increased generation of foliage and enhancement in stem and root growth which is also evidenced by higher net assimilation and relative growth rate. The increase was highest at flowering stage with a concomitant increase in net photosynthetic rate but showed reduction in respiration rate and stomatal conductance. The increase in net photosynthesis further resulted in higher accumulation of sugars, non-structural carbohydrates and starch in leaves in elevated CO₂ grown plants. Larger accumulation of biomass was observed in root as compared to other plant parts. However, the species specific differences were reflected in the accumulation of biomass, grain yield and gas exchange phenomena, wherein the greater response was invariably found in RH-30 (Brassica juncea) as compared to Pusa Gold (Brassica campestris). The present study may prove beneficial to understand crop responses to future climatic conditions and suggest efficient adaptive strategies from crop management perspectives.     

Pancreatic adenocarcinoma: a pilot study of quantitative perfusion and diffusion-weighted breath-hold magnetic resonance imaging

Purpose

To confirm the feasibility of breath-hold DCE-MRI and DWI at 3T to obtain the intra-abdominal quantitative physiologic parameters, K ^trans, k _ep, and ADC, in patients with untreated pancreatic ductal adenocarcinomas.

Methods

Diffusion-weighted single-shot echo-planar imaging (DW-SS-EPI) and dynamic contrast-enhanced (DCE) MRI were used for 16 patients with newly diagnosed biopsy-proven pancreatic ductal adenocarcinomas. K ^trans, k _ep, and apparent diffusion coefficient (ADC) values of pancreatic tumors, non-tumor adjacent pancreatic parenchyma (NAP), liver metastases, and normal liver tissues were quantitated and statistically compared.

Results

Fourteen patients were able to adequately hold their breath for DCE-MRI, and 15 patients for DW-SS-EPI. Four patients had liver metastases within the 6 cm of Z axis coverage centered on the pancreatic primary tumors. K ^trans values (10^?3 min^?1) of primary pancreatic tumors, NAP, liver metastases, and normal liver tissues were 7.3 ± 4.2 (mean ± SD), 25.8 ± 14.9, 8.1 ± 5.9, and 45.1 ± 15.6, respectively, k _ep values (10^?2 min^?1) were 3.0 ± 0.9, 7.4 ± 3.1, 5.2 ± 2.0, and 12.1 ± 2.8, respectively, and ADC values (10^?3 mm²/s) were 1.3 ± 0.2, 1.6 ± 0.3, 1.1 ± 0.1, and 1.3 ± 0.1, respectively. K ^trans, k _ep, and ADC values of primary pancreatic tumors were significantly lower than those of NAP (p < 0.05), while K ^trans and k _ep values of liver metastases were significantly lower than those of normal liver tissues (p < 0.05).

Conclusions

3T breath-hold quantitative physiologic MRI is a feasible technique that can be applied to a majority of patients with pancreatic adenocarcinomas.     

Assessing Lung Inflammation After Nanoparticle Inhalation Using 2-deoxy-2-[18F]fluoro-d-glucose Positron Emission Tomography Imaging

Purpose

The aim of the present study was to evaluate the use of 2-deoxy-2-[¹⁸F]fluoro-d-glucose ([¹⁸F]FDG) as a noninvasive strategy to assess the time course of inflammatory processes after inhalation of ZnO nanoparticles (NPs) in rats.

Procedures

Healthy, male Sprague–Dawley rats (n?=?30) were divided in two groups of 15 animals each. Animals from one group (n?=?15) were submitted to ZnO NPs inhalation in a chamber (10 nm to 4 μm particle size; maximum in number concentration, ～200 nm; concentration?=?245 mg/m³). Animals from the other group (n?=?15, sham group) were also exposed following the same procedure, but no NPs were introduced into the chamber. Six animals per group were submitted to [¹⁸F]FDG-positron emission tomography (PET) studies at days 1, 7, and 28 after exposition, and the [¹⁸F]FDG influx constant (K _i ) for the lungs was calculated using Patlak graphical analysis and an image derived blood input function. Nine animals per group were killed at 1, 7 and 28 days after exposure (n?=?3 per group and time point), and the lungs were harvested and submitted to immunohistochemical and histological analysis.

Results

Significantly higher mean whole-lung K _i values were obtained for animals exposed to NPs at days 1 and 7 after exposure (0.0045?±?0.0016 min^?1 and 0.0047?±?0.0015 min^?1, respectively) compared to controls (0.0024?±?0.0010 min^?1 and 0.0019?±?0.0011 min^?1 at 1 and 7 days, respectively). The K _i value for exposed animals dropped to 0.0023?±?0.0010 min^?1 at day 28. This value was not significantly different from the values obtained at 1, 7, and 28 days for the control group. Immunofluorescence staining on lung tissue slices from animals exposed to ZnO NPs showed an increase in CD11b reactivity at days 1 and 7, followed by a decrease in CD11b positive cells at 28 days. Hematoxylin–eosin staining showed histological alterations in the exposed lungs to ZnO NPs at days 1 and 7 that recovered at 28 days postexposure.

Conclusions

The [¹⁸F]FDG influx rate constant (K _i ) could be determined by PET using Patlak analysis and a corrected image derived input function. Higher K _i values were obtained for animals exposed to ZnO NPs at days 1 and 7 after exposition. These results were in good concordance with immunohistochemical assays performed on harvested tissue samples.     

Multi-scale sample entropy of electroencephalography during sevoflurane anesthesia

The electroencephalogram (EEG) has been widely applied in the assessment of depth of anesthesia (DoA). Recent research has found that multi-scale EEG analysis describes brain dynamics better than traditional non-linear methods. In this study, we have adopted a modified sample entropy (MSpEn) method to analyze anesthetic EEG series as a measure of DoA. EEG data from a previous study consisting of 19 adult subjects undergoing sevoflurane anesthesia were used in the present investigation. In addition to the modified sample entropy method, the well-established EEG indices approximate entropy (ApEn), response entropy (RE), and state entropy (SE) were also computed for comparison. Pharmacokinetic/pharmacodynamic modeling and prediction probability (P _k ) were used to assess and compare the performance of the four methods for tracking anesthetic concentration. The influence of the number of scales on MSpEn was also investigated using a linear regression model. MSpEn correlated closely with anesthetic effect. The P _k (0.83 ± 0.05, mean ± SD) and the coefficient of determination R ² (0.87 ± 0.21) for the relationship between MSpEn and sevoflurane effect site concentration were highest for MSpEn (P _k : RE = 0.73 ± 0.08, SE = 0.72 ± 0.07, ApEn = 0.81 ± 0.04; R ²: RE = 0.75 ± 0.08, SE = 0.64 ± 0.09, ApEn = 0.81 ± 0.10). Scales 1, 3 and 5 tended to make the greatest contribution to MSpEn. For this data set, the MSpEn is superior to the ApEn, the RE and the SE for tracking drug concentration change during sevoflurane anesthesia. It is suggested that the MSpEn may be further studied for application in clinical monitoring of DoA.     

Long-term estimates of live above-ground tree carbon stocks and net change in managed uneven-aged mixed species forests of sub-tropical Queensland,Australia

Estimates of carbon stocks and their annual change for extensive Australian sub-tropical forests are based on indirect estimates or on data derived from temperate forests. We estimated live above-ground tree carbon (LAC) stocks at landscape level from 355?000 measurements of 94?127 tree stems from 604 permanently monitored plots representing 2.6 million ha of managed uneven-aged mixed-species native forests in sub-tropical Queensland. These plots were established between 1936 and 1998 and re-measured every 2 to 10 years up to 2011. Landscapes were represented by 16 broad vegetation groups growing across a mean annual rainfall range of 500 to 2000 mm. Landscape-mean LAC stocks varied from 20.8 ± 4.3 t C ha^?1 in inland eucalypt woodlands to 146.4 ± 11.1 t C ha^?1 in coastal wet tall open forests. Landscape maximum LAC stock, defined as the mean of maximum LAC stocks over the entire measurement history for a specified landscape under prevailing environmental conditions and disturbance regimes, including sustainable forest management, ranged from 34.0 ± 7.2 t C ha^?1 in inland eucalypt woodlands to 154.9 ± 19.4 t C ha^?1 in coastal wet tall open forests. Annual live above-ground net carbon flux (C-flux) across all forests types ranged from 0.46 to 2.92 t C ha^?1 y^?1 with an overall mean of 0.95 t C ha^?1 y^?1 (n = 2067). Comparison of our results with Intergovernmental Panel on Climate Change (IPCC) estimates shows that in all cases, except for the sub-tropical steppe, the IPCC over-estimated stocks by between 13% and 34%. Conversely, the IPCC estimated C-fluxes were between 14% and 40% less than the Queensland estimates. These results extend statistically valid estimates of landscape LAC stocks and fluxes to the sub-tropical regions of Australia.     

Apixaban, an oral, direct and highly selective factor Xa inhibitor: in vitro, antithrombotic and antihemostatic studies

Summary. Background: Apixaban is an oral, direct and highly selective factor Xa (FXa) inhibitor in late‐stage clinical development for the prevention and treatment of thromboembolic diseases. Objective: We evaluated the in vitro properties of apixaban and its in vivo activities in rabbit models of thrombosis and hemostasis. Methods: Studies were conducted in arteriovenous‐shunt thrombosis (AVST), venous thrombosis (VT), electrically mediated carotid arterial thrombosis (ECAT) and cuticle bleeding time (BT) models. Results: In vitro, apixaban is potent and selective, with a K_i of 0.08 nm for human FXa. It exhibited species difference in FXa inhibition [FXa K_i (nm ): 0.16, rabbit; 1.3, rat; 1.7, dog] and anticoagulation [EC_2× (μm , concentration required to double the prothrombin time): 3.6, human; 2.3, rabbit; 7.9, rat; 6.7, dog]. Apixaban at 10 μm did not alter human and rabbit platelet aggregation to ADP, γ‐thrombin, and collagen. In vivo, the values for antithrombotic ED₅₀ (dose that reduced thrombus weight or increased blood flow by 50% of the control) in AVST, VT and ECAT and the values for BT ED_3× (dose that increased BT by 3‐fold) were 0.27 ± 0.03, 0.11 ± 0.03, 0.07 ± 0.02 and > 3 mg kg^?1 h^?1 i.v. for apixaban, 0.05 ± 0.01, 0.05 ± 0.01, 0.27 ± 0.08 and > 3 mg kg^?1 h^?1 i.v. for the indirect FXa inhibitor fondaparinux, and 0.53 ± 0.04, 0.27 ± 0.01, 0.08 ± 0.01 and 0.70 ± 0.07 mg kg^?1 day^?1 p.o. for the oral anticoagulant warfarin, respectively. Conclusions: In summary, apixaban was effective in the prevention of experimental thrombosis at doses that preserve hemostasis in rabbits.     

Determining the optical properties of a gelatin‑TiO(2) phantom at 780 nm

Tissue phantoms play a central role in validating biomedical imaging techniques. Here we employ a series of methods that aim to fully determine the optical properties, i.e., the refractive index n, absorption coefficient μ_a, transport mean free path ?^?, and scattering coefficient μ_s of a TiO₂ in gelatin phantom intended for use in optoacoustic imaging. For the determination of the key parameters μ_a and ?^?, we employ a variant of time of flight measurements, where fiber optodes are immersed into the phantom to minimize the influence of boundaries. The robustness of the method was verified with Monte Carlo simulations, where the experimentally obtained values served as input parameters for the simulations. The excellent agreement between simulations and experiments confirmed the reliability of the results. The parameters determined at 780 nm are n = 1.359(±0.002), μ^′_s = 1/?^? = 0.22(±0.02)?mm^-1, μ_a= 0.0053(+0.0006-0.0003)?mm^-1, and μ_s = 2.86( ± 0.04)?mm^-1. The asymmetry parameter g obtained from the parameters ?^? and μ^′_s is 0.93, which indicates that the scattering entities are not bare TiO₂ particles but large sparse clusters. The interaction between the scattering particles and the gelatin matrix should be taken into account when developing such phantoms.OCIS codes: (170.3660) Light propagation in tissues, (170.6935) Tissue characterization, (290.1990) Diffusion, (290.4210) Multiple scattering     

Acute saline infusion induces extracellular acidification and activation of the Na+/H+ exchanger in man

The effect of acute expansion of the extracellular fluid volume (ECV) with isotonic (0.9%) saline on the activity of the lymphocyte Na⁺/H⁺ antiport (NHE) was studied in a total of 18 healthy volunteers. Saline was infused at a constant rate so that 4 mmol kg^?1 b.w. was administered over 2 h. NHE activity was measured by quantifying cytosolic pH (pH_i) recovery following acidification of the cells with propionic acid and by pH clamping at various pH_i values between 7.2 and 5.8 using nigericin. Both methods demonstrate NHE activation associated with intravenous saline infusion, the kinetic difference being a marked decrease in the Hill coefficient n from 3.28 ± 0.21 (SEM) to 2.22 ± 0.11 in the absence of changes in baseline pH_i (7.14 ± 0.02 vs. 7.08 ± 0.02; P = 0.15), V_max (42.8 ± 2.7 vs. 48.1 ± 2.8 mmol L^?1 min^?1; P = 0.08) and pK (6.32 ± 0.04 vs. 6.35 ± 0.02). NHE activation was associated with significant decreases in serum chloride (P = 0.016), calcium (P = 0.008), total cholesterol (P = 0.008), low-density lipoproteins (P = 0.016) and high-density lipoproteins (P = 0.008). Moreover, saline infusion induced extracellular acidification with a decrease in pH from 7.39 ± 0.01 to 7.37 ± 0.01 (P = 0.016), HCO₃^? from 23.3 ± 0.43 mmol L^?1 to 21.3 ± 0.25 mmol L^?1 (P = 0.008) and base excess from ?1.03 ± 0.38 mmol L^?1 to ?3.00 ± 0.31 mmol L^?1 (P = 0.008). Our results show for the first time that acute ECV expansion with isotonic saline is followed by an activation of the lymphocyte NHE. The underlying mechanism(s) remain to be investigated. However, the demonstration in our study of marked changes in acid–base balance induced by acute saline points to a possible inter-relationship of antiporter activation and extracellular acidification.